Calcium-dependent changes in potassium currents in guinea-pig coronary artery smooth muscle cells after acute cobalt loading in vivo

2004 ◽  
Vol 449 (1) ◽  
pp. 16-25 ◽  
Author(s):  
Kiril Hristov ◽  
Iskra Altankova ◽  
Hristo Gagov ◽  
Thomas Bolton ◽  
Kiril K. Boev ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Coronary Artery ◽  
Guinea Pig ◽  
Smooth Muscle Cells ◽  
Potassium Currents ◽  
Muscle Cells ◽  
Calcium Dependent ◽  
Cobalt Loading ◽  
Pig Coronary Artery

Abstract 604: Targeting Cx43 Prevents Growth Factor-Induced Phenotypic Change in Pig Coronary Artery Smooth Muscle Cells

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Christos E Chadjichristos ◽  
Sandrine Morel ◽  
Jean-Paul Derouette ◽  
Anne Brisset ◽  
Isabelle Roth ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Coronary Artery ◽  
Growth Factor ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Phenotypic Change ◽  
Intimal Thickening ◽  
Cx43 Expression ◽  
Junction Protein ◽  
Pig Coronary Artery

Percutaneous coronary intervention (PCI) is commonly used to treat atherosclerotic coronary arteries, but its efficacy is limited by restenosis at the site of the intervention. We reported previously that reducing the expression of the gap junction protein connexin43 (Cx43) in mice restricted neointima formation after acute vascular injury by limiting the inflammatory response as well as the proliferation and migration of smooth muscle cells (SMCs) towards the damaged site. SMC populations isolated from the pig coronary artery exhibit distinct phenotypes: spindle-shaped (S) and rhomboid (R). S-SMCs are predominant in the normal media, whereas R-SMCs are recovered in higher proportion from stent-induced intimal thickening suggesting that they participate in the intimal thickening. Here, we further investigate the relationship between connexin expression and SMC phenotype using the distinct types of pig coronary artery SMCs. We show that Cx40 was highly expressed in normal media of porcine coronary artery in vivo, whereas Cx43 was barely detectable. In contrast, Cx40 was down-regulated and Cx43 was markedly up-regulated in SMCs of stent-induced intimal thickening. In vitro, S-SMCs expressed Cx40 and Cx43. Cx43 expression was increased in R-SMCs and these cells no longer expressed Cx40. When S-SMCs were treated with 10 ng/ml platelet-derived growth factor (PDGF-BB) they acquired a rhomboid phenotype and their migratory activity increased (from 40.3±5.7 to 185.9±27.3 migrating cells; mean±SEM, N=4, P<0.01). These changes were accompanied by an increase in Cx43 and loss of Cx40 expression. Importantly, PDGF-BB-induced phenotypic change of S-SMCs was prevented by reducing Cx43 expression with 100 uM antisense for Cx43. Thus, Cx43 antisense-treated SMCs retained their typical elongated appearance and the expression of some SMC differentiation markers, such as alpha-SM actin, whereas the appearance of S100A4, a typical marker of R-SMCs, was prevented. In conclusion, limiting Cx43 expression in SMCs prevents growth factor-induced changes towards a deleterious phenotype. Our findings suggest that Cx43 might be an additional target for local delivery strategies aimed at reducing restenosis after PCI.

scholarly journals Biosafety and Efficacy Evaluation of a Biodegradable Magnesium based Drug-eluting Stent in Porcine Coronary Artery

2020 ◽  
Author(s):  
Jinzhou Zhu ◽  
Xiyuan Zhang ◽  
Jialin Niu ◽  
Yongjuan Shi ◽  
Zhengbin Zhu ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Coronary Artery ◽  
Smooth Muscle Cells ◽  
Porcine Model ◽  
Muscle Cells ◽  
Comparable Efficacy ◽  
Drug Eluting Stent ◽  
Drug Eluting

Abstract Although drug-eluting stent (DES) has become the standard for percutaneous coronary interventions (PCI) based revascularization, stent thrombosis has emerged as a major cause of death and morbidity for those clinical commonly used permanent stents. Drug-eluting bioresorbable stent (BRS) was thus developed as an alternative to DES, which can be completely absorbed after its therapeutic period. Among them, magnesium (Mg) based BRS has attracted great attention due to its suitable mechanical properties, innovative chemical features and well-proven biocompatibility. In the present work, a Mg–Nd–Zn-Zr (JDBM) based drug-eluting BRS loaded with rapamycin was prepared, and its biosafety and efficacy for coronary artery stenosis were evaluated via in vitro and in vivo experiments. The smooth muscle cells adhesion of PDLLA/RAPA coated alloy and the rapamycin pharmacokinetics of JDBM BRS were first assessed in vitro. JDBM BRS and commercial DES Firehawk were then implanted in the coronary arteries of a porcine model. Neointimal hyperplasia was evaluated at 30, 90, and 180 days, and re-endothelialization was evaluated at 30 days. Furthermore, Micro-CT and optical coherence tomography (OCT) analysis were performed to evaluate the technical feasibility and biocompatibility of JDBM alloy based drug-eluting BRS in vivo. The results showed the inhibition ability of PDLLA/RAPA coated JDBM to smooth muscle cells adhesion and moderate drug release rate of JDBM BRS, demonstrating good anti-restenosis ability in vitro. In vivo, low local and systemic risks of JDBM alloy based BRS was demonstrated in the porcine model. We also showed that this novel BRS was associated with a comparable efficacy profile and high anti-restenosis performance. These findings may confer long term advantages for the use of this BRS over a traditional DES.

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